CAS 1492-18-8|Folinic acid (Calcium)

Introduction：Basic information about CAS 1492-18-8|Folinic acid (Calcium), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Folinic acid (Calcium) BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Synonyms

Common Name	Folinic acid (Calcium)
CAS Number	1492-18-8	Molecular Weight	511.501
Density	/	Boiling Point	/
Molecular Formula	C₂₀H₂₁CaN₇O₇	Melting Point	240-250ºC
MSDS	ChineseUSA	Flash Point	/
Symbol	GHS07, GHS08	Signal Word	Danger

Names

Name	Folinic acid calcium salt hydrate
Synonym	More Synonyms

Folinic acid (Calcium) BiologicalActivity

Description	Leucovorin Calcium is a reduced folic acid.IC50 Value: 30 μM for zcSHMT and70 μM for zmSHMT [2]Target: Antifolatein vitro: Increasing concentrations of leucovorin (N5-CHO-THF) inhibit both zcSHMT and hcSHMT activities substantially, yet to a lesser extent than zmSHMT. The IC50 of leucovorin is approximately 30 μM for zcSHMT and higher than 70 μM for zmSHMT. The differential inhibition is evident with the presence of 10 μM leucovorin, the concentration estimated in serum in a high-dose leucovorin rescue regimen [2].in vivo: Following intravenous administration, peak plasma concentrations of (6R) LV, (6S) LV, and 5-CH3 THF were 148 +/- 32, 59.1 +/- 22, and 17.8 +/- 17 microM, respectively. During oral administration of LV, virtually no (6S) LV appeared in the plasma. Steady-state plasma concentrations of (6R) LV and 5-CH3 THF were approximately 1.5 +/- 0.23 and 2.8 +/- 0.41 microM, respectively [1]. 24 fasted subjects were given 4 of a series of 5 single test doses between 20 and 100 mg, at 1-week intervals, of 5-formyl-THF as an oral solution of leucovorin calcium. Six separate subjects received 200 mg iv and po in a 2-way crossover. Blood and urine samples were collected over 24 hours for differential microbiological folate assays using Lactobacillus casei and Streptococcus faecalis. Using L casei activity to measure total serum folates, the area under the concentration-time curve from 0 to infinite time (AUC[0-infinity]) was calculated. Relative bioavailabilities were 78%, 62%, 49%, and 42% for the 40-, 60-, 80-, and 100-mg doses, respectively [3].Clinical trial: Leucovorin and Fluorouracil With or Without SU-5416 in Treating Patients With Metastatic Colorectal Cancer . Phase 3
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>AntifolateResearch Areas >>Cancer
References	[1]. Schilsky RL, Ratain MJ. Clinical pharmacokinetics of high-dose leucovorin calcium after intravenous and oral administration. J Natl Cancer Inst. 1990 Sep 5;82(17):1411-5. [2]. Chang WN, Tsai JN, Chen BH, Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37. [3]. McGuire BW, Sia LL, Haynes JD, Absorption kinetics of orally administered leucovorin calcium. NCI Monogr. 1987;(5):47-56.

Description

Leucovorin Calcium is a reduced folic acid.IC50 Value: 30 μM for zcSHMT and70 μM for zmSHMT [2]Target: Antifolatein vitro: Increasing concentrations of leucovorin (N5-CHO-THF) inhibit both zcSHMT and hcSHMT activities substantially, yet to a lesser extent than zmSHMT. The IC50 of leucovorin is approximately 30 μM for zcSHMT and higher than 70 μM for zmSHMT. The differential inhibition is evident with the presence of 10 μM leucovorin, the concentration estimated in serum in a high-dose leucovorin rescue regimen [2].in vivo: Following intravenous administration, peak plasma concentrations of (6R) LV, (6S) LV, and 5-CH3 THF were 148 +/- 32, 59.1 +/- 22, and 17.8 +/- 17 microM, respectively. During oral administration of LV, virtually no (6S) LV appeared in the plasma. Steady-state plasma concentrations of (6R) LV and 5-CH3 THF were approximately 1.5 +/- 0.23 and 2.8 +/- 0.41 microM, respectively [1]. 24 fasted subjects were given 4 of a series of 5 single test doses between 20 and 100 mg, at 1-week intervals, of 5-formyl-THF as an oral solution of leucovorin calcium. Six separate subjects received 200 mg iv and po in a 2-way crossover. Blood and urine samples were collected over 24 hours for differential microbiological folate assays using Lactobacillus casei and Streptococcus faecalis. Using L casei activity to measure total serum folates, the area under the concentration-time curve from 0 to infinite time (AUC[0-infinity]) was calculated. Relative bioavailabilities were 78%, 62%, 49%, and 42% for the 40-, 60-, 80-, and 100-mg doses, respectively [3].Clinical trial: Leucovorin and Fluorouracil With or Without SU-5416 in Treating Patients With Metastatic Colorectal Cancer . Phase 3

Related Catalog

Signaling Pathways >>Cell Cycle/DNA Damage >>AntifolateResearch Areas >>Cancer

References

[1]. Schilsky RL, Ratain MJ. Clinical pharmacokinetics of high-dose leucovorin calcium after intravenous and oral administration. J Natl Cancer Inst. 1990 Sep 5;82(17):1411-5.

[2]. Chang WN, Tsai JN, Chen BH, Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2127-37.

[3]. McGuire BW, Sia LL, Haynes JD, Absorption kinetics of orally administered leucovorin calcium. NCI Monogr. 1987;(5):47-56.

Chemical & Physical Properties

Melting Point	240-250ºC
Molecular Formula	C₂₀H₂₁CaN₇O₇
Molecular Weight	511.501
Exact Mass	511.112823
PSA	198.10000
LogP	1.41100
InChIKey	BZPWXVJDMRBCMD-ZEDZUCNESA-N
SMILES	Nc1nc2c(c(=O)[nH]1)N(C=O)C(CNc1ccc(C(=O)NC(CCC(=O)O)C(=O)O)cc1)CN2.[Ca]

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MA0600500

CAS REGISTRY NUMBER :: 1492-18-8

LAST UPDATED :: 199706

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C20-H21-N7-O7.Ca

MOLECULAR WEIGHT :: 511.56

WISWESSER LINE NOTATION :: T66 BN DN GN JM&TJ CZ EQ GVH I1MR DVMYVO2VO &-NA-

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >8 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1063 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >7 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1036 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,93,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 732 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,910,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6060 No. of Facilities: 103 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 3686 (estimated) No. of Female Employees: 2084 (estimated)

Safety Information

Symbol	GHS07, GHS08
Signal Word	Danger
Hazard Statements	H315-H317-H319-H334-H335
Precautionary Statements	P261-P280-P305 + P351 + P338-P342 + P311
Hazard Codes	Xn:Harmful
Risk Phrases	R36/37/38;R42/43
Safety Phrases	S26-S36-S36/37-S22
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	MA0600500
HS Code	2942000000

Customs

HS Code	2942000000

Synonyms

L-N-(p-(((2-Amino-5-formyl-5,6,7,8-tetrahydro-3-hydroxy-6-pteridinyl)methyl)amino)benzoyl)glutamic Acid Calcium Salt (1:1)

calcium, [L-glutamato(2-)-κO,κO, N-[4-[[(2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-]-

(2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydroptéridin-6-yl)méthyl]amino}phényl)carbonyl]amino}pentanedioate de calcium

[N-(4-{[(2-Amino-5-formyl-4-hydroxy-5,6,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamato(2-)-κO,O]calcium

5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic acid calcium salt

Calcium folinate

5-HCO-H4PteGlu

Leucovorin calcium salt

Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)amino]pentanedioate

MFCD00006704

Calcium-(2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)carbonyl]amino}pentandioat

Calcium Folinate Hydrate

5-Formyl-5,6,7,8-tetrahydrofolic acid calcium salt

Folinic Acid Calcium Salt Hydrate

Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-hydroxy-5,6,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)amino]pentanedioate

Leucovorin calcium

Calcium (2S)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl)methyl]amino}benzoyl)amino]pentanedioate

[N-(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamato(2-)-κO,O]calcium

EINECS 216-082-8

Folinic acid calcium salt

calcium (2S)-2-{[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)carbonyl]amino}pentanedioate

(+)-L-Folinic Acid Calcium Salt

Citrovorum factor calcium salt

L-Glutamic acid, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-, calcium salt (1:1)

calcium, [L-glutamato(2-)-κO,κO, N-[4-[[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-]-

[N-(4-{[(2-Amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl)-D-glutamato(2-)-κO,O]calcium

Folinic acid (Calcium)

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